Objectives To estimate the proportion of live-attenuated influenza vaccine (LAIV) doses administered beyond expiry date in children and adolescents during influenza seasons 2013–2014 and 2014–2015 in the UK. Design This was a retrospective cohort study. Two cohorts of children and adolescents who received LAIV from 1 September 2013 to 31 March 2014 and from 1 September 2014 to 31 March 2015 and aged 2–17 years at time of LAIV administration were identified from the Clinical Practice Research Datalink (CPRD). Setting More than 500 primary care practices in the UK. Population Proportions of vaccine doses administered beyond expiry date were assessed among 47 396 and 67 099 LAIV recipients with a documented vaccine lot identifier in influenza seasons 2013–2014 and 2014–2015, respectively. Intervention None. Main outcome measure Administrations of expired LAIV were ascertained by comparison of vaccination dates in CPRD records with expiration dates in AstraZeneca/MedImmune lot distribution data. Results Overall, 245 LAIV recipients, 80 in 2013–2014 and 165 in 2014–2015, received a dose after its expiration date, yielding proportion estimates of 1.7 per 1000 doses (95% CI 1.3 to 2.1) in season 2013–2014 and 2.5 per 1000 doses (95% CI 2.1 to 2.8) in season 2014–2015. This proportion increased above 1.0% after December during each season. Most (84% in influenza season 2013–2014 and 59% in influenza season 2014–2015) received an expired dose <30 days after its expiration date. The proportion was higher in London (relative risk 1.93 (95% CI 1.25 to 2.99)) and when the number of LAIV recipients registered in the practice was lower than the median number per practice (relative risk 2.69 (95% CI 1.99 to 3.62)). Conclusions Administration of expired LAIV doses occurs infrequently.

Background: Vasculitides have been reported as adverse events following immunization (AEFI) following various vaccines. We describe reports of vasculitis to three international spontaneous reporting systems.Methods: All spontaneous reports of vasculitis following immunization between January 2003 and June 2014 were retrieved from Eudravigilance (EV), the Vaccine Adverse Event Reporting System (VAERS), and VigiBase (R). A Standard MedDRA Query (SMQ) for vasculitis was used and vaccine types were categorized using the Anatomical Therapeutic Chemical classification system. We performed a descriptive analysis by source, sex, age, country, time to onset, vaccine, and type of vasculitis.Results: We retrieved 1797 reports of vasculitis in EV, 1171 in VAERS, and 2606 in VigiBase (R). Vasculitis was predominantly reported in children aged 1-17 years, and less frequently in the elderly (>65 years). The generic term "vasculitis" was the most frequently reported AEFI" in this category across the three databases (range 21.9% to 27.5% of all reported vasculitis for vaccines). For the more specific terms, Henoch-Schoenlein Purpura (HSP) was most frequently reported, (19.1% on average), followed by Kawasaki disease (10) (16.1% on average) and polymyalgia rheumatica (PMR) (9.2% on average). Less frequently reported subtypes were cutaneous vasculitis (CuV), vasculitis of the central nervous system (CNS-V), and Behcet's syndrome (BS). HSP, PMR and CuV were more frequently reported with influenza vaccines: on average in 29.3% for HSP reports, 61.5% for PMR reports and in 39.2% for CuV reports KD was reported with pneumococcal vaccines in 32.0% of KD reports and with rotavirus vaccines in more than 20% of KD reports. BS was most frequently reported after hepatitis and HPV vaccines and CNS-V after HPV vaccines.Conclusion: Similar reporting patterns of vasculitides were observed in different databases. Implementation of standardized case definitions for specific vasculitides could improve overall data quality and comparability of reports. Published by Elsevier Ltd.

Background: Several types of vasculitis have been observed and reported in temporal association with the administration of various vaccines. A systematic review of current evidence is lacking.Objective: This systematic literature review aimed to assess available evidence and current reporting practice of vasculitides as adverse events following immunization (AEFI).Methods: We reviewed the literature from 1st January 1994 to 30th June 2014. This review comprises randomized controlled trials, observational studies, case series, case reports, reviews and comments regardless of vaccine and target population.Results: The initial search resulted in the identification of 6656 articles. Of these, 157 articles were assessed for eligibility and 75 studies were considered for analysis, including 6 retrospective/observational studies, 2 randomized controlled trials, 7 reviews, 11 case series, 46 case reports and 3 comments. Most of the larger, higher quality studies found no causal association between vaccination and subsequent development of vasculitis, including several studies on Kawasaki disease and Henoch-Schonlein purpura (IgA vasculitis). Smaller case series reported a few cases of vasculitis following BCG and vaccines against influenza and hepatitis. Only 24% of the articles reported using a case definition of vasculitis.Conclusions: Existing literature does not allow establishing a causative link between vaccination and vasculitides. Further investigations were strengthened by the use of standardized case definitions and methods for data collection, analysis and presentation to improve data comparability and interpretation of vasculitis cases following immunization, Published by Elsevier Ltd.

Assess whether Medicare data are useful for monitoring tissue allograft safety and utilization. We used health care claims (billing) data from 2007 for 35 million fee-for-service Medicare beneficiaries, a predominantly elderly population. Using search terms for transplant-related procedures, we generated lists of ICD-9-CM and CPT(®) codes and assessed the frequency of selected allograft procedures. Step 1 used inpatient data and ICD-9-CM procedure codes. Step 2 added non-institutional provider (e.g., physician) claims, outpatient institutional claims, and CPT codes. We assembled preliminary lists of diagnosis codes for infections after selected allograft procedures. Many ICD-9-CM codes were ambiguous as to whether the procedure involved an allograft. Among 1.3 million persons with a procedure ascertained using the list of ICD-9-CM codes, only 1,886 claims clearly involved an allograft. CPT codes enabled better ascertainment of some allograft procedures (over 17,000 persons had corneal transplants and over 2,700 had allograft skin transplants). For spinal fusion procedures, CPT codes improved specificity for allografts; of nearly 100,000 patients with ICD-9-CM codes for spinal fusions, more than 34,000 had CPT codes indicating allograft use. Monitoring infrequent events (infections) after infrequent exposures (tissue allografts) requires large study populations. A strength of the large Medicare databases is the substantial number of certain allograft procedures. Limitations include lack of clinical detail and donor information. Medicare data can potentially augment passive reporting systems and may be useful for monitoring tissue allograft safety and utilization where codes clearly identify allograft use and coding algorithms can effectively screen for infections.

Processors distributed about 1.5 million human tissue allografts in the U.S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA implemented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplantations. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after implementation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, examining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001-2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospitalizations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not confirm that the reported infections were caused by suspect tissues; most reports may represent routine post-surgical infections not actually due to allografts.

Processors distributed about 1.5 million human tissue allografts in the U.S. in 2007. The potential for transmitting infections through allografts concerns clinicians and patients. In 2005, FDA imple- mented Current Good Tissue Practice (CGTP) rules requiring tissue establishments to report to FDA certain serious infections after allograft transplanta- tions. We describe infection reports following tissue transplants received by FDA from 2005 through June, 2010, and compare reporting before and after imple- mentation of CGTP rules. We identified reports received by FDA from January 2001 through June, 2010, for infections in human tissue recipients, exam- ining the reports by tissue type, organism, time to onset, severity, and reporter characteristics. Among 562 reports, 83 (20.8/year) were received from 2001-2004, before the CGTP rules, 43 in the 2005 transition year, and 436 (96.9/year) from 2006 through June, 2010, after the rules. Tissue processors accounted for 84.2% of reports submitted after the rules, compared to 26.5% previously. Bacterial infections were the most commonly reported organisms before (64.6%) and after (62.2%) the new rules. Afterward, 2.5% (11) of reports described deaths, and 33.7% (147) involved hospitalizations. Before the rules, 13% (11) described deaths, and another 72% involved hospital- izations. Reports received by the FDA quadrupled since 2005, suggesting that CGTP regulations have contributed to increased reporting and improved tissue safety surveillance. However, these data do not con- firm that the reported infections were caused by suspect tissues; most reports may represent routine post- surgical infections not actually due to allografts.

Background: Babesiosis is a known transfusion-transmitted disease risk and there is no FDA-licensed test for donor screening. Approximately 80 transfusion-transmitted cases have been reported 1979 through 2008. This research evaluated the Babesia-related transfusion events reported to the Food and Drug Administration (FDA) with particular focus on numbers and characteristics of transfusion-related babesiosis fatality reports. Methods: Data were collected from FDA's Blood Collection and Transfusion Fatality Reporting and Biological Product Deviation Reports (BPDRs) surveillance systems. Results: From 2005 through 2008, the FDA received 10 transfusion-related babesiosis fatality reports after only one prior report in 1998. Recipients presented with symptoms 2.5 to 9 weeks after transfusion of implicated red blood cell units. In recent years, FDA has also seen an increase in Babesia-related BPDRs involving donors with post donation illness and reports of potential transfusion-transmitted disease. Most reports submitted to the FDA implicate B. microti. Conclusion: The reports received by the FDA indicate Babesia infection may be a rare but increasing risk to the blood supply. Without a licensed screening test to prevent these transmissions, enhanced clinician awareness of the possibility of babesiosis in febrile, recent transfusion recipients may facilitate prompt diagnosis, improved prognosis, and more timely investigations to interdict infected units. Prompt reporting of babesiosis donor and transfusion-related events assists the FDA in assessing the scope of this risk and developing appropriate public health control measures. Disclaimer: The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. Abstracts for SupplementInternational Journal of Infectious DiseasesVol. 14Preview Full-Text PDF Open Archive

We reviewed thrombocytopenia (TP) reports to the US Vaccine Adverse Event Reporting System (VAERS). We examined TP patterns for differences in single versus multiple immunization reports, presence of a live viral vaccine, seriousness, age, and interval to symptom onset. We found 1510 reports of possible TP and after exclusions evaluated 1440 for possible causes. Most (1078; 75%) met the regulatory definition of a serious adverse event. TP was reported after inactivated and live viral vaccines. Platelet counts <10×10(9)/L were reported. Identified vaccines could be prioritized for hypothesis-testing studies.

Background. Human babesiosis is an illness with clinical manifestations that range from asymptomatic to fatal. Although babesiosis is not nationally notifiable, the US incidence appears to be increasing. Babesia infection is a transfusion-transmissable disease. An estimated 70 cases were reported during 1979-2007; most of these cases were reported during the past decade.Methods. We queried the 3 following US Food and Drug Administration safety surveillance systems to assess trends in babesiosis reporting since 1997: fatality reports for blood donors and transfusion recipients, the Adverse Event Reporting System (which includes MedWatch), and the Biological Product Deviations Reporting system. We analyzed fatality reports for time frames, clinical presentations, and patient and donor demographic characteristics.Results. Eight of 9 deaths due to transfusion-transmitted babesiosis that were reported since 1997 occurred within the past 3 years (2005-2007). Four implicated donors and 5 patients lived in areas where Babesia infection is not endemic. Increasing numbers of Biological Product Deviations Reports were submitted to the US Food and Drug Administration over the past decade; the Adverse Event Reporting System received no reports.Conclusions. After nearly a decade with no reported death due to transfusion-transmitted babesiosis, the US Food and Drug Administration received 8 reports from November 2005 onward. The increased numbers of deaths reported and Biological Product Deviations Reports suggest an increasing incidence of transfusion-transmitted babesiosis. Physicians should consider babesiosis in the differential diagnosis in immunocompromised, febrile patients with a history of recent transfusion, even in areas where Babesia infection is not endemic. Accurate and timely reporting of babesiosis-related donor and transfusion events assists the US Food and Drug Administration in developing appropriate public health-control measures.

Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide enough details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' websites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events.